A genome-wide association scan (GWAS) for mean telomere length within the COGS project: identified loci show little association with hormone-related cancer risk.
Pooley KA., Bojesen SE., Weischer M., Nielsen SF., Thompson D., Amin Al Olama A., Michailidou K., Tyrer JP., Benlloch S., Brown J., Audley T., Luben R., Khaw KT., Neal DE., Hamdy FC., Donovan JL., Kote-Jarai Z., Baynes C., Shah M., Bolla MK., Wang Q., Dennis J., Dicks E., Yang R., Rudolph A., Schildkraut J., Chang-Claude J., Burwinkel B., Chenevix-Trench G., Pharoah PD., Berchuck A., Eeles RA., Easton DF., Dunning AM., Nordestgaard BG.
Mean telomere length (TL) in blood cells is heritable and has been reported to be associated with risks of several diseases, including cancer. We conducted a meta-analysis of three GWAS for TL (total n=2240) and selected 1629 variants for replication via the "iCOGS" custom genotyping array. All ∼200 000 iCOGS variants were analysed with TL, and those displaying associations in healthy controls (n = 15 065) were further tested in breast cancer cases (n = 11 024). We found a novel TL association (Ptrend < 4 × 10(-10)) at 3p14.4 close to PXK and evidence (Ptrend < 7 × 10(-7)) for TL loci at 6p22.1 (ZNF311) and 20q11.2 (BCL2L1). We additionally confirmed (Ptrend < 5 × 10(-14)) the previously reported loci at 3q26.2 (TERC), 5p15.3 (TERT) and 10q24.3 (OBFC1) and found supportive evidence (Ptrend < 5 × 10(-4)) for the published loci at 2p16.2 (ACYP2), 4q32.2 (NAF1) and 20q13.3 (RTEL1). SNPs tagging these loci explain TL differences of up to 731 bp (corresponding to 18% of total TL in healthy individuals), however, they display little direct evidence for association with breast, ovarian or prostate cancer risks.